Acetylcysteine in Patients Undergoing Cardiac Imaging

Chicago—A drug intended to prevent contrast-induced kidney damage in patients undergoing cardiac imaging failed to work in a large, randomized trial. Acetylcysteine failed to reduce the short-term risks of contrast-induced nephropathy or any other clinically relevant outcomes at 30 days, even among high-risk subgroups. Trial results were presented at the 2010 American Heart Association Scientific Sessions. At least 45 previous studies of acetylcysteine reported inconsistent results for use of acetylcysteine in preventing contrast-induced nephropathy, but these studies were underpowered or had methodologic problems. The ACT (Acetylcysteine for the Prevention of Contrast-Induced Nephropathy) trial was a well-designed study that should lay this question to rest. The study has implications for the healthcare system, because acetylcysteine is used in a proportion of patients to prevent contrast-induced nephropathy with no justification. In fact, 1 study in Michigan showed that 10% of all patients and 30% of those with chronic renal insufficiency received acetylcysteine when undergoing percutaneous coronary intervention (PCI). Although the drug is not expensive, ancillary costs involved in its use before PCI can be expensive. “We all like simple solutions, but the largest acetylcysteine randomized trial conducted to date failed to show a benefit. Results of this high-quality study may help inform clinical practice and update guidelines,” said lead author Otavio Berwanger, MD, Research Institute at the Hospital do Coração in Sao Paulo, Brazil. The study enrolled 2308 patients undergoing an angiographic procedure with ≥1 of the following risk factors: age >70 years, chronic renal failure, diabetes mellitus, heart failure or left ventricular ejection fraction <45%, or shock. “This is a broad population of patients at risk for contrast-induced nephropathy,” Dr. Berwanger said. Patients were randomized to receive acetylcysteine 1200 mg orally twice a day for 2 doses before and 2 doses after the procedure or matching placebo. The groups had similar baseline characteristics. Mean age was 68 years, about 38% were female, about 15% had chronic renal failure, about 60% had diabetes, about 9% had heart failure, and about 0.2% had shock. About 68% underwent coronary diagnostic angiography and about 32% had PCI. About 95% of patients were compliant with all 4 doses of study drug. No significant difference was observed between the 2 treatments for the primary end point of contrast-induced nephropathy (12.7% in each arm), serum creatinine elevation of >0.5 mg/dL (3.9% in the acetylcysteine arm vs 3.8% in the placebo arm), and doubling of serum creatinine (1.1% in the acetylcysteine arm vs 1.5% in the placebo arm). At 30 days, no significant difference was observed between treatment groups for mortality, need for dialysis, and cardiovascular mortality. Low rates of adverse events were observed, occurring in 7.6% of patients in the acetylcysteine arm and 7% of the placebo arm. Serious adverse events, such as stroke, sepsis, and acute pulmonary edema, were reported in 1.3% and 2.2%, respectively, of the acetylcysteine and placebo arms. A subgroup analysis failed to reveal benefit for acetylcysteine in any subgroup, including age ≥70 years and <70 years, sex, presence or absence of diabetes, presence or absence of elevated serum creatinine, and type of contrast agent. The mechanisms responsible for contrast-induced nephropathy are not well defined. The damage is often reversible, but some patients who develop it may need dialysis, and it can even cause death. The highest risk is in the first 3 days following injection of contrast. Dr. Berwanger said more research is needed to identify or develop a safer agent. Another study, ACT II, is being planned by the Brazilian researchers.